Non-invasive identification of slow conducting anatomical isthmuses in patients with tetralogy of Fallot by 3D late gadolinium enhancement cardiovascular magnetic resonance imaging

Background Patients with repaired tetralogy of Fallot (rTOF) remain at risk of sustained monomorphic ventricular tachycardia (SMVT) related to slow-conducting anatomical isthmuses (SCAI). Invasive electroanatomical mapping (EAM) is the only available method to identify SCAI (SCAI EAM ). We aimed to determine rTOF-specific high signal intensity threshold values (HSI t ) to identify abnormal myocardium by 3D late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) and assess the performance of LGE-CMR to non-invasively identify SCAI EAM . Methods Consecutive rTOF patients who underwent right ventricular EAM (RV-EAM) and 3D LGE-CMR were included (2012-2021). A SCAI EAM was defined as an anatomical isthmus (AI) with conduction velocity (CV) <0.5 m/s. LGE-CMR-derived 3D RV reconstructions were merged with 3D RV-EAM data. The HSI t was determined based on the comparison of local bipolar voltages (BV) and the corresponding local SI using ROC analysis. An abnormal AI on LGE-CMR (Abnormal AI CMR ) was defined as AI showing continuous high SI (>HSI t ) between anatomical boundaries. Results Forty-eight rTOF patients (34±16 years, 58% male) were included. Of 107 AIs on EAM (AI1 and 3 in all, AI2 in 11), 78 were normal-conducting AI EAM (NCAI EAM ), 22 were SCAI EAM (SCAI EAM 2 in 2 and SCAI EAM 3 in 20), and 7 were blocked AI EAM 3. All 14 induced SMVTs were related to SCAI EAM 3. A total of 9240 EAM points were analyzed. HSI t was 42% of the maximal SI (AUC 0.80; sensitivity, 74%; specificity, 78%). On 3D-CMR RV construction, all 29 SCAI EAM or Blocked AI EAM were identified as abnormal AI CMR . Among the 78 NCAI EAM , 70 were normal AI CMR and 8 were abnormal AI CMR . The sensitivity and specificity of 3D LGE-CMR for identifying SCAI EAM or blocked AI EAM were 100% and 90% (29/29 and 70/78), respectively. Among patients with NCAI EAM 3 (n=28), those with abnormal AI CMR 3 (n=6) had significantly lower BV and slower CV compared with those with normal AI CMR 3 (n=22) (BV, 1.91 [1.62-2.60] vs. 3.45 mV [2.22-5.67]; CV, 0.69 [0.62-0.81] vs, 0.95 m/s [0.82-1.09]; both P<0.01). Conclusion 3D LGE-CMR can identify SCAI with excellent sensitivity and specificity and may identify diseased AI3 even before critical conduction delay occurs, which may enable non-invasive risk stratification of VT and may refine patient selection for invasive EAM. What is new? rTOF-specific high signal intensity threshold (HSI t ) value on 3D LGE-CMR to identify abnormal myocardium was determined by direct comparison between 9240 superimposed 3D EAM points and corresponding local signal intensity on the 3D CMR-derived reconstruction. The newly proposed method of CMR image analysis using the obtained HSI t showed an excellent interobserver agreement and could identify SCAI or blocked AI with 100% sensitivity and 90% specificity. Compared to patients with NCAI EAM and normal AI CMR (true negative CMR), those with NCAI EAM but abnormal AI CMR (false positive CMR) had already significantly lower BV and CV on EAM. What are the clinical implications? The newly proposed technique of 3D LGE-CMR image analysis may allow for non-invasive and serial risk stratification of VT in patients with rTOF and can refine patient selection for invasive EAM and concomitant ablation.